The objective of this Phase II project is to further develop a newly designed hollow fiber bioreactor. The applicant claims the bioreactor can support five times more viable mammalian cells/ml than existing hollow fiber bioreactors. The phase I project demonstrated that a bioreactor constructed with an internal oxygenation membrane can support mammalian cells in culture. The Phase II project would complete the design of the bioreactor and generate the data required to design and develop a series of mammalian cell culture systems based on this concept. The Phase III plan is to commercialize a series of instruments, from small bench-top scale to large scale production systems, that would meet the needs of the diagnostic and therapeutic protein manufacturers. The Phase II project has two major areas of research: The design and development of a spirally-wrapped version of the new reactor's capabilities with respect to the growth of attachment dependent cells. For the former work a number of NMR imaging and spectroscopic techniques would be developed that would allow bioreactor performance to be evaluated non-invasively. The applicants states the NMR techniques may be widely applicable to other hollow fiber bioreactors and high cell density perfusion reactors.